Antiviral composition against flavivirus

a technology of antiviral composition and flavivirus, applied in the field of composition, can solve the problems of no approved antiviral therapy or treatment of most of the flavivirus infection, many deaths and afflicted millions of people, and threaten almost 2.5 billion people living, and achieve the effect of reducing the yield of the virus

Inactive Publication Date: 2015-11-24
UNIVERSITI MALAYA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention aims to provide a composition that can prevent or treat infections caused by flaviviruses, such as dengue virus or Japanese encephalitis virus. The composition has the ability to inhibit virus replication, reduce the yield of viruses, and even kill them. Furthermore, the composition can also prevent virus attachment to host cells.

Problems solved by technology

Dengue has caused many deaths and afflicted millions of people annually and threatened almost 2.5 billion people living in the regions.
To date, there is no approved therapeutics or antiviral therapy for the treatment of most of the flavivirus infection if not all of them, including dengue.
There is no effective antiviral that can help to reduce dengue virus load in patients to prevent the severe manifestation of dengue, DHF or DSS.
Effort to prevent dengue using vaccine is plagued with many potential issues and risks.

Method used

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  • Antiviral composition against flavivirus
  • Antiviral composition against flavivirus
  • Antiviral composition against flavivirus

Examples

Experimental program
Comparison scheme
Effect test

example a

[0063]Example A shows a composition of baicalein that exhibits prophylactic effects on dengue virus type-2 (DENV-2).

[0064]In order to determine the prophylactic anti-dengue activity of baicalein, different concentrations of baicalein (6.25 μg / ml, 12.50 μg / ml, 25.0 μg / ml, and 50.0 μg / ml) were added to the Vero cell monolayers five hours before adding virus. After five hours of pre-infection treatment, the cells were washed twice with phosphate-buffered saline (PBS). Then, 200 FFU (focus-forming units) of dengue virus type-2 (DENV-2) was inoculated to the cells to produce infected cells. The infected cells were incubated at 37° C. for one hour. Then the infected cells were washed two times with PBS to eliminate the unadsorped viruses. Growth medium (the growing medium is but not limited to Eagle's minimal essential medium; EMEM) was supplemented with 2% fetal bovine serum (FBS), 1 mM non-essential amino acid solution, 1 mM L-glutamine solution, and 1.5% carboxymethyl cellulose (CMC) s...

example b

[0066]Example B shows a composition of baicalein that shows inhibition of DENV-2 attachment to host cells.

[0067]Inhibition of DENV-2 attachment to host cells was evaluated by adding different concentrations (3.12 μg / ml, 6.25 μg / ml, 12.5 μg / ml, 25.0 μg / ml, and 50.0 μg / ml) of baicalein to Vero cells simultaneously with 200 FFU DENV-2. Then, the infected Vero cells were incubated at 37° C. for one hour in the presence of the respective concentration of baicalein. Following after, the infected Vero cells were washed two times using sterile PBS. Growth medium supplemented with 2% fetal bovine serum (FBS), 1 mM non-essential amino acid solution, 1 mM L-glutamine solution, and 1.5% carboxymethyl cellulose (CMC) solution) was added to the infected cells in the microplate. The microplate was incubated at 37° C. for four days. The number of viral foci formed and the viral RNA level were determined. The amount of viral RNA synthesis was determined using quantitative real time polymerase chain ...

example c

[0069]Example C shows a composition of baicalein that shows antiviral activity on dengue virus type-2 (DENV-2) replication when added post-infection.

[0070]In order to evaluate the antiviral activity of baicalein after virus attachment to cells, virus inoculum consisting of 200 FFU DENV-2 was added to the monolayer Vero cells and the virus was allowed to adsorp to the Vero cells for one hour at a temperature of 37° C. Unadsorped viruses were removed by rinsing the Vero cells with sterile PBS for two times. Different concentrations of baicalein (3.12 μg / ml, 6.25 μg / ml, 12.5 μg / ml, 25.0 μg / ml, and 50.0 μg / ml) were mixed with 1.5% CMC containing cell-growth medium supplemented with 2% FBS respectively before incubated at 37° C. for four days. Then, the number of viral foci and viral RNA level were measured.

[0071]FIGS. 3(a) and (b) showed that 50 μg / ml of baicalein reduced the number of dengue virus foci formed by 78.3% and decreased the level of DENV-2 RNA production by 84.9%±2.15 compa...

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Abstract

The present invention relates to a composition having antiviral activity for prophylaxis or treatment of flavivirus infection or a disease resulting therefrom in humans or animals, characterized in that said composition consisting of baicalein, or analogs, or derivatives thereof. The composition may further comprise a pharmaceutically acceptable carrier. The antiviral activity may include inhibition of virus attachment to host cells, inhibition of intracellular virus replication and direct virucidal activity. The flavivirus may comprise dengue virus type-1, dengue virus type-2, dengue virus type-3, dengue virus type-4 and Japanese encephalitis virus.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]This invention relates to a composition having antiviral activity for prophylaxis or treatment of positive-stranded RNA virus infection or a disease, and more particularly to the composition comprising flavonoid baicalein for prophylaxis or treatment of a flavivirus infection.[0003]2. Description of Related Arts[0004]The positive-stranded RNA virus including flavivirus family comprises many medically important viruses which include dengue, a serious mosquito-borne disease common in the tropics and sub-tropical regions of the world. Dengue has caused many deaths and afflicted millions of people annually and threatened almost 2.5 billion people living in the regions. It is amongst the most rapidly spreading mosquito-borne viral infection.[0005]Dengue is caused by dengue virus a member of the genus flavivirus, family Flaviviridae, a positive-strand RNA virus. Other common medically important virus in this family includes J...

Claims

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Application Information

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Patent Type & AuthorityPatents(United States)
IPC IPC(8): A61K31/352A61K36/539
CPCA61K36/539A61K31/352A61P31/12Y02A50/30
InventorABU BAKAR, SAZALY
OwnerUNIVERSITI MALAYA